August 2020 BusinessInsider; Remdesivir is as close to famous as an antiviral treatment gets.
The drug is the only one that has gotten emergency authorization from the FDA as a coronavirus treatment.
Gilead Sciences began developing remdesivir as a treatment for Ebola in 2009, and though it was never approved for that purpose, the drug showed early promise for COVID-19 patients.
In May, a study published in the New England Journal of Medicine found that COVID-19 patients treated with remdesivir had an average recovery time of 11 days, compared to 15 days for patients who had received a placebo.
But new research published in the Journal of the American Medical Association found that remdesivir didn’t significantly improve outcomes for patients. Patients put on a 10-day course of remdesivir didn’t improve more than patients who didn’t get the drug; they also died at the same rates. And although patients on remdesivir did report fewer severe symptoms of COVID-19 overall, they also experienced more minor to moderate symptoms and side effects.
Patients who received remdesivir didn’t fare much better than patients who didn’t
Remdesivir works by inhibiting enzymes that play a key role in the replication of viruses, including coronaviruses. Although it wasn’t found to be very effective against Ebola, it didn’t cause negative side effects either — the drug was shown to be safe.
So starting in 2014, Gilead began investigating remdesivir’s use as a treatment for coronaviruses like SARS and MERS. Then after the new coronavirus emerged, the company started clinical trials to determine whether the drug was effective against COVID-19.
The FDA issued an emergency authorization for remdesivir on May 1, and Gilead donated its drug supply for two months after that. Then in June, the company announced it would charge governments of developed countries $2,340 for a five-day course.
But the new study raises questions about whether buying large quantities of the drug is worth it.
The researchers looked at a group of 584 people with confirmed cases of COVID-19. All were at least 12 years old and had been hospitalized with moderate COVID-19 pneumonia. The patients were divided into three groups: One group received a 10-day course of remdesivir, the second received a five-day course, and the third were treated without remdesivir.
The researchers then compared the patients’ outcomes in two ways. They charted how many adverse effects patients had — including fatal results and negative symptoms like nausea — and measured how much patients improved. They also tracked the lengths of hospital stays, recovery times, and how long patients required respiratory support.
After 11 days, patients in the 10-day group did not seem to fare significantly better than patients treated without the drug over the same length of time. In fact, the remdesivir-treated groups saw more mild to moderate side effects and symptoms than those who didn’t take the drug, though they had fewer severe symptoms overall. Patients who took remdesivir were more likely to report nausea, headaches, and hypokalemia: a condition caused by low potassium that can cause heart irregularities.
The results showed little difference in how long the three groups spent in the hospital or on oxygen therapy. After 28 days, 2% of patients in both the 10-day remdesivir group and the non-remdesivir group had died.
In the five-day group, however, only 1% died after 28 days. Still, the study authors deemed that finding to be of “uncertain clinical importance,” since most people in the 10-day group left the hospital before finishing the full course of their treatment (the median length of their treatment was just six days).
The study raises more questions than it answers
Taison Bell, an infectious-disease physician at the University of Virginia who was involved in the May study, said the new study doesn’t necessarily show that remdesivir is ineffective.
Instead, he said, it suggests more work must be done to understand which patients might benefit from the drug. The May study found that remdesivir worked best for those who required moderate to low amounts of supplemental oxygen, Bell said.
“There’s a sweet spot,” he added. “You need to target patients who are sick enough, but not too sick. But we need to do further studies to determine what that patient population is.”
Bell also noted that the study offers evidence that longer treatments of remdesivir may not be more effective than shorter ones — “certainly good news when considering the challenges of manufacturing and distributing remdesivir,” he said.
However, in a commentary accompanying the new study, Erin McCreary and Derek Angus, two researchers at the University of Pittsburgh Medical Center, said the new findings raise a question about “whether the drug is less efficacious than hoped.”
But they, too, noted several key differences between this research and the prior study that might explain why the results differ.
First, McCreary and Angus wrote, the May study was larger than this recent one, so may have been better equipped to find small differences between participants. Second, the earlier study compared remdesivir to a placebo, while this new study compared remdesivir to a range of less specific, non-remdesivir treatments. Some patients received hydroxychloroquine, for instance.
The patient groups were also different: As Bell noted, those recruited for the May study had more severe respiratory symptoms than those in the new JAMA study. However, since the May study found that since the people who benefited most from remdesivir tended to require low amounts of supplemental oxygen, that difference might not matter.
Ultimately, McCreary and Angus concluded, it’s still unclear whether remdesivir is more effective than cheaper, more widely available options, such as the steroid dexamethasone, which has shown early promise in clinical trials.
“Whether remdesivir offers incremental benefit over corticosteroids, which are widely available and inexpensive, is unknown,” they wrote.